Fundamental for a better understanding of the functional role of sensory transmission in the neuronal circuitry which regulates gastrointestinal functions is the establishment of the morphological organization and chemical messengers of the sensory afferent innervation of the enteric nervous system, which comprises the neuronal elements innervating the alimentary canal. Afferent mechanisms are important in the activity of the gut and afferent visceral input plays a considerably more complex role than pain transmission, participating in visceral regulation and coordination through different neuronal pathways. The main objective of the proposed studies is to analyze the sensory afferent innervation of the gut, using chemical markers which have been shown to be suitable of labeling subpopulations of sensory neurons and terminals, such as neuropeptides, with a particular emphasis on calcitonin gene-related peptide (CGRP) which appears to be the most ubiquitous peptide sensory marker described to date, and histochemical, immunohistochemical and molecular biological approaches. The proposed studies are directed to 1) define the origin and fine structure of CGRP innervation of the rat gastrointestinal tract, 2) investigate the relationship of CGRP neurons and terminals with those containing other peptide sensory markers, such as substance P (SP) or the newly discovered and structurally related tachykinins, substance K and neuromedin K, using region specific antisera, and with other non-peptide sensory markers, such as the enzyme fluoride- resistant acid phosphatase (FRAP) and carbohydrate epitopes and 3) determine the sites of biosynthesis of CGRP and SP or related tachykinins using Northern blot and in situ hybridization techniques. These studies will provide important information on the functional organization of sensory afferent innervation of the gut and a morphological basis for a better understanding of the complex neural interactions which integrate and coordinate gastrointestinal functions.